It is proposed to synthesize analogs of the cholelitholytic bile acids, chenodeoxycholic acid and ursodeoxycholic acid, in order to develop new compounds with increased resistance to degradation by the intestinal bacterial flora and hepatic enzymes, increased cholelitholytic activity and reduced hepatoxicity. The biological stability of the bile acid analogs, and their inhibitory effect on the bacterial 7-dehydroxylase, will be examined in cultures of fecal bacteria and with purified bacterial 7-dehydroxylase. Resistance to hepatic degradation will be studied in the isolated perfused rabbit liver. Analogs with adequate biologic stability and significant biliary excretion will be tested in animal models of cholesterol cholelithiasis (hamster, squirrel monkey). It is proposed to identify structural features of known bile acids and analogs associated with specific effects on the prevension or regression of gallstones, and on several parameters of cholesterol bile acid metabolism (cholesterol balance, rate-limiting enzymes of cholesterol metabolism (HMG-CoA reductase, cholesterol 7Alpha-hydroxylase) biliary lipids and bile acids, tissue sterol levels and composition of gallstones).